PulmCrit- APRV: Resurrection of the open-lung strategy?

Open-lung ventilation refers to the concept of recruiting the lung and then ventilating gently with small tidal volumes, to avoid either over-distension or atelectotrauma (lung damage from cyclical opening/closing of alveoli). ARDSnet low tidal-volume ventilation was a success for the open lung concept. However, subsequent efforts to advance this concept further have floundered, with several failed attempts to manipulate PEEP. A recent editorial in JAMA speculated about whether the open-lung strategy is dead (Sahetya 2017).

The obstacle to opening the lung using conventional ventilation is basic arithmetic. Opening the lung requires more PEEP. Driving pressure can be reduced a bit, but it can't be reduced too much without causing severe hypoventilation. Therefore, increasing the PEEP forces the plateau pressure to rise (figure below). You can't have your cake and eat it too (high PEEP and low plateau).

APRV solves this problem by flipping the pressure curve upside-down. A single pressure (P-High) is used both to recruit the lungs and also as the driving pressure for exhalation. This allows achieving a high mean airway pressure with a relatively low plateau pressure:

Great idea, little hard evidence.

APRV is conceptually very appealing, for example:

APRV is better tolerated than conventional low tidal-volume ventilation, obviating the need for paralytics and deep sedation. This may avoid complications such as myopathy and delirium. APRV is compatible with early-mobility initiatives (some videos from Maryland Shock Trauma feature patients walking on APRV).

Diaphragmatic activity promotes recruitment and ventilation of the lung bases.

Ventilator-induced lung injury might be a product of the tidal volume multiplied by the frequency of ventilation (which determines the total energy absorbed by the lung; figure below). Since APRV involves relatively infrequent release breaths and a lower minute ventilation than conventional ventilation, this should make APRV more lung-protective (1).

Lack of evidence in the medical ICU (most experience originates from the surgical ICU).

Use of large tidal volumes in the release breaths (>8-10 cc/kg) seems to violate the principles of lung-protective ventilation.

Weaning APRV can be a tedious process of gradually reducing the pressure.

This has led to a paradoxical situation, where APRV is often used in surgical ICUs but not medical ICUs. APRV may be viewed as a “new” technique by medical intensivists, whereas it's been used for decades in surgical ICUs with great results (Andrews 2013). A fresh RCT may help resolve this…

Zhou et al 2017

This is by far the largest RCT of APRV to date. Patients with ARDS were randomized to receive APRV versus low tidal-volume ventilation. The primary endpoint was the number of ventilator-free days, which was dramatically greater in the APRV group. Patients treated with APRV required fewer additional therapies (proning, paralysis, and recruitment).

APRV was well tolerated hemodynamically, with higher blood pressure and lower heart rates. Patients with APRV were more awake, receiving less sedative and pain medication:

This study does have limitations:

Single-center design.

Open-label (unavoidable, given differences between APRV and conventional ventilation).

Within the APRV group, respiratory therapists were allowed to titrate analgesics and sedatives to promote spontaneous breathing. More intensive titration of sedating medications may have promoted lower levels of sedation and earlier extubation.

The APRV protocol may require more effort, causing patients to receive more attention. However, this phenomenon might be generalizable to actual practice as well.

Devil in the details

Although APRV is often considered as a single “intervention,” there are innumerable ways to perform APRV. Several components of the APRV protocol used by these authors deserve attention:

#1: Limiting P-High

When patients are placed on conventional ventilation, they often wind up in the vicious cycle shown below. The sicker they are, the higher the pressures they require. Higher pressures lead to worsening lung injury, and so on as the ventilator beats up the lung:

The protocol these authors used did some clever things to avoid this:

The P-High was capped at 30 cm. This prevents patients from ever being exposed to extremely high levels of pressure.

Persistent hypoxemia was managed by increasing P-Low. Thus, the sickest patients would receive higher P-Low, which would decrease the driving pressure and decrease the tidal volume (maximizing lung protection).

Capping P-High at 30 cm is controversial. It is appealing, because it could avoid barotrauma and cor pulmonale. However, it is possible that a P-High above 30 cm might be required to manage patients with supermorbid obesity. A recent survey of respiratory therapists from various institutions showed that practice regarding P-High is enormously variable (below, Miller 2017). This survey does suggest that capping P-High at 30 cm is possible, because it was the practice at nine hospitals.

#2: Use of a positive P-low

Unlike many current APRV protocols, these authors used P-Low values above zero (starting at 5 cm, then titrated). Using a positive P-Low value may make this more lung-protective, because it could avoid de-recruitment and reduce the driving pressure. However, it is likely that using a P-low of zero with appropriately short T-low would achieve the same result.

#3: Achievement of low tidal volumes

One notable aspect of this protocol is that there were no significant differences in tidal volume comparing APRV versus conventional low tidal-volume ventilation (e.g. on the first day after randomization, both groups had an average tidal volume of 7 cc/kg). Their ability to achieve low tidal volumes using APRV likely reflects a combination of capping P-High, increasing P-Low, and meticulous titration of T-Low. Some APRV protocols generate large tidal volumes (>8-10 cc/kg), which has been an ongoing source of concern. The ability to achieve low tidal volume ventilation with APRV makes this protocol much more appealing because it adheres better to the principles of lung-protective ventilation (2).

In general, modern principles of ventilator liberation emphasize the use of a comfortable, non-fatiguing level of ventilator support punctuated by a daily spontaneous breathing trial. Patients who fail the spontaneous breathing trial are immediately returned to full ventilator support.

The authors point out that most APRV protocols currently violate this concept. Usually, APRV is gradually weaned with a slow reduction in the level of ventilator support. This is potentially suboptimal:

For a patient who isn't ready to wean, gradually reducing the ventilator support risks leaving the patient for long periods of time at an inadequate level of support. This may cause insidious diaphragmatic fatigue, setting the patient back substantially (severe muscle fatigue often takes 1-2 days to recover).

For a patient who is ready to wean, gradually reducing support at an arbitrary rate may delay extubation.

Therefore, the authors weaned patients by performing intermittent conventional spontaneous breathing trials (5-7 cm pressure support and 5 cm PEEP) after the patients were on a low level of APRV (20 cm P-Hi and 40% FiO2). This is a very aggressive approach, which would cause most providers to worry about de-recruitment. Nonetheless, in their hands it seemed to work.

The ideal way to wean APRV remains unclear, requiring further study. It's possible that a dichotomy exists regarding the ability to adjust P-High:

While the patient is acutely ill, P-High must be adjusted very slowly to avoid de-recruitment.

After the patient has stabilized for a few days and is recovering, APRV may be weaned off more rapidly.

#5. Early initiation of APRV

This study used APRV early in the patient's hospital course (within 48 hours of intubation). This may maximize the benefit of APRV for a few reasons:

APRV works best when patients are relatively awake and not paralyzed. Alternatively, when APRV is used as a rescue mode, it is often applied to patients who are deeply sedated and paralyzed.

The open-lung theory suggests that APRV may be more lung-protective than conventional ventilation. If so, it would make sense to initiate APRV early (rather than after the lungs have been injured by conventional mechanical ventilation).

This isn't a new concept: other authors have previously discussed that APRV ideally shouldn't be used as a salvage modality (Chatburn 2016). Indeed, emerging evidence supports the use of APRV up-front to stabilize the lung and prevent ARDS (Andrews 2013, Sadowitz 2016).

How should we set APRV?

It remains unclear exactly how we should set APRV. One could argue that since Zhou has reported the best clinical outcomes in an RCT, we should replicate their protocol. However, some elements of their protocol may require further validation before widespread application (e.g. transitioning a patient directly from P-Hi of 20 cm to a conventional spontaneous breathing trial).

One attempt to create a guideline for APRV is shown here. This strives to combine some more traditional elements of APRV protocols with some of the more attractive features of Zhou's protocol (e.g. limiting the P-High and achieving low tidal volumes). Based on positive outcomes from both Maryland Shock Trauma and Zhou et al. using different protocols, it's likely that a variety of different strategies would work fine.

Zhou et al. 2017 is the largest RCT to be performed on APRV. It shows benefit compared to conventional low tidal-volume ventilation in terms of liberation from the ventilator and fewer tracheostomies (figure below).

This is a single-center study with significant limitations. It is premature to conclude that APRV is definitely superior to low tidal-volume ventilation. However, this study suggests that APRV is a legitimate front-line ventilator mode for patients with ARDS.

Early use of APRV may allow avoidance of paralysis and deep sedation, facilitating more rapid weaning from ventilation. It's also possible that early application of APRV could avoid progressive ventilator-induced lung injury.

The details of exactly how APRV is implemented are relevant. These authors avoided high peak pressure and high tidal volumes, which may have improved hemodynamic stability and lung protection.

These authors weaned APRV very abruptly. Although this requires further study, it suggests that after the lung injury is improving and the patient has stabilized, APRV may be weaned relatively fast.

Notes

APRV ventilation takes advantage of both bulk gas flow and also diffusion of CO2 into the dead space while the lung is held open. This diffusion reduces the dead space, making ventilation more efficient and thereby reducing the necessary minute ventilation. Reducing the minute ventilation reduces the work the patient needs to expend and also reduces the energy that lung tissue must absorb during ventilation.

Incidentally, this suggests a different way to protocolize APRV which might be simpler and safer than most current protocols. Rather than hyper-sophisticated strategies for adjusting T-Low (e.g. based on peak expiratory flow rate angle), it would be simpler to adjust T-Low to target a tidal volume of 6-8 ml/kg. That is simple, easy, and supported by a fair amount of evidence (compared to many APRV protocols which are confusing, complicated, and not strongly evidence-based).

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Tom

This is interesting. I’ve been a big fan of APRV for most of my career, but mostly in the setting of a centre that is afraid of peep > 15. When we started using the esophageal balloon, we discovered that high peep wasn’t as scary as we thought, and APRV fell off. I think this is the case for this study. The ventilator they used doesn’t do APRV very well. The 840 has a synchronization window at the end of inspiration and exhalation that will trigger or cycle the breath to achieve more comfort for the patient. In practice what this means that that relatively tachypneic patients will get shorter Thighs. The Thighs of this study are already short by conventional APRV standards — the longest being about 5.5 seconds. When you get up to a set RR of 16 — which was their max — the Thigh drops to about 3.25 seconds. The control group was the ARDSnet low peep table protocol. I think this is probably a suboptimal control, because it doesn’t seem to me that many centres use a strict ARDSnet protocol. I think peep is being guided with esophageal balloons, EIT, or VD/VT calculations, and I… Read more »

Thanks for some very interesting comments. I think that standard ARDSnet low-tidal volume ventilation was the appropriate comparison. The history of mechanical ventilation is full of examples of things which seemed to work, but weren’t borne out in RCTs (e.g. HFOV, higher PEEP tables, ART trial). Currently ARDSnet is the evidence-based standard approach to ventilation in ARDS. I think that most centers in the United States are using ARDSnet and don’t have access to EIT or esophageal balloons. So whatever is being proposed as superior (whether it is esophageal balloons or APRV) should ideally be compared to ARDSnet before it can be accepted as a superior approach. I’d argue that probably the greatest weakness of this study was that it was a single-center design, and that it should ideally be replicated with a multi-center study. Of course, the way critical care goes it may be a decade before that happens.

Thank you very much for this splendid review. In supplement 2 reviewers comment on a decelerating flow instead of a square flow in some VCV-pictures. Do you think the applied waveform (and flow) can be a confounder?

Thanks. It’s impossible to say with certainty, which is frustrating (almost by necessity, there were *lots* of differences between the two ventilation strategies, which makes it impossible to assign outcome to any specific feature). However, I doubt that a square waveform vs. decelerating flow would make much difference.

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tom fiero

cool review, Josh. my brother is a pulm/crit doc in virginia, and i’ll send this his way. thank you.
tom

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Leon Boudourakis

Josh. Tks for post. While setting t low based on volumes may be simpler, it doesn’t make physiological sense. It’s also potentially very dangerous. Comparing low tidal ardsnet assumptions for patients on positive pressure modes to the idea that low volumes are somehow also needed for protective strategy on APRV is comparing apples to oranges. Release volumes on aprv don’t matter (i mean…. if they are like crazy then something is set wrong!). Release Volumes released on aprv increase in just a few hours in patients placed on aprv who have recruitable alveoli and is reflective of increased FRC…. not improperly set t low…. The reason why we do low tidal on ARDS patients is to not over distend on a positive pressure mode like volume control – mostly cuz the alveoli that distend are predominantly anterior and upper west lung zone areas (eg most he volume goes there) With aprv the physiology is totally different.. it’s a pressure mode with long periods of pressure and thus the “air” is more evenly distributed. The only reason you would over distend anything is cuz your p high is set too high. In short, the release volumes on aprv being higher than… Read more »

Dear Josh
Please can I use your fantastic infographic on this trial for a presentation I am delivering on conventional Mx of ARDS – will appropriately reference you of course!
Many thanks
Caz Sampson

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mohammed abbasi

The open lung strategy has been debunked by several studies, the latest being the ART trial. Acc to Gattinoni atelectrauma is not clinically relevant and there are no human studies to suggest otherwise. Lung rest should be the main focus. if APRV works it’s because pts are less sedated and able to initiate breaths so ofcourse they’ll come off the vent faster.

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Mohammed Abbasi

The entire theory of open lung strategy rests on decreasing atelectrauma-however if you look at gattinoni’s latest landmark paper on this he showed that the amount of lung units opening and closing is the same regardless of PEEP 5 vs PEEP 15!

I’m not sure that we’re comparing apples to apples here. There is a significant difference between an “open lung strategy” in the Cressoni ICM paper and an APRV open lung strategy. Likely, the above authors found no significant difference in open lung tissue for PEEP of 5 and PEEP of 15 is that they were still using a traditional ventilation technique of a short I time – relying on the peep alone to keep the alveoli open. An inspiratory phase of .8-1.2 seconds is not long enough to even allow gas to exchange properly in severely diseased lungs. APRV seeks to use CPAP levels of pressure to maintain an open lung at higher pressures. The Phigh (or CPAP level) is maintained for AT LEAST 4-6 seconds, to facilitate gas exchange and gas flow through intra-alveolar channels. We certainly allow some spontaneous breaths when patients can take them effectively, but aside from that we allow very short releases within the CPAP phase, to assist with more CO2 removal. These releases are designed on the patient’s specific needs, and are short enough to maintain recruitment during the length of the phase. It’s an interesting concept to use end inspiratory and end expiratory… Read more »

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mohammed abbasi

Thank you for responding. You’re right APRV is a different mode and you can’t directly compare to other trials but the concept is the same. Let me expound on my previous assertion – the open lung strategy claims atelectrauma is dangerous and must be prevented. Cressoni’s article did not show that open lung tissue was the same at PEEP 5 and PEEP 15 (at Pplat 30) as you assert, in fact they found that higher PEEP kept more lung tissue open, however the amount of tissue that “opens and closes” stayed the same. The point is – to keep the lung fully open you need very high pressures which risks barotrauma and hemodynamic compromise. You also say that inspiratory phase of .8-1.2 seconds is too short to allow for gas exchange in ards, please cite some evidence to support this. Gattinoni showed that ARDS is a baby lung not a stiff lung, and that gas exchange is compromised due to edema and lung collapse. Inspiration therefore must overcome those forces to recruit alevoli for ventilation, PEEP keeps alveoli from collapsing at end inspiration, similarly APRV uses higher PEEP for longer cycles to achieve this. Gas exchange is not necessarily better… Read more »

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Leon

Little confused why the digression. Let me say it again: Altering t low to aim for any volume (eg low tidal) not only doesn’t make physiological sense….. even if it did, it’s not practically possible! Release volumes fluctuate in the real world quite a bit! Sometimes the release is during a spontaneous expiration, sometimes if during a spontaneous inspiration, sometimes it’s in the middle of an inspiration-exoneration, and sometimes u can t tell. Point is if u were really trying to titration your t low to a volume – you would be adjusting it every 10 seconds! I may be exaggerating for sake of the point. 🙂 Also, for a sub group of patients (usually patients with poor compliance), titration gets to a volume of 300-400 will be very dangerous if the end exploratory flow rate is <50 of the peak inspiratory flow rate. In short this is BAD BAD BAS baro and volume Trauma every release despite the “low volume”. While tittering t low to volume may be appealing cuz it’s so simple, please please don’t do this – instead just don’t do aprv do some other mode. also, Dr Abass….. it’s refreshing to hear a fellow be so… Read more »